Lgr5+ telocytes are a signaling source at the intestinal villus tip

Keren Bahar Halpern, Hassan Massalha, Rachel K. Zwick, Andreas E. Moor, David Castillo-Azofeifa, Milena Rozenberg, Lydia Farack, Adi Egozi, Dan R. Miller, Inna Averbukh, Yotam Harnik, Noa Weinberg-Corem, Frederic J. Sauvage, Ido Amit, Ophir D. Klein, Michal Shoshkes-Carmel () and Shalev Itzkovitz ()
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Keren Bahar Halpern: Weizmann Institute of Science
Hassan Massalha: Weizmann Institute of Science
Rachel K. Zwick: University of California
Andreas E. Moor: University of Zurich
David Castillo-Azofeifa: University of California
Milena Rozenberg: Weizmann Institute of Science
Lydia Farack: Weizmann Institute of Science
Adi Egozi: Weizmann Institute of Science
Dan R. Miller: Weizmann Institute of Science
Inna Averbukh: Weizmann Institute of Science
Yotam Harnik: Weizmann Institute of Science
Noa Weinberg-Corem: The Hebrew University Hadassah Medical School
Frederic J. Sauvage: Genentech
Ido Amit: Weizmann Institute of Science
Ophir D. Klein: University of California
Michal Shoshkes-Carmel: The Hebrew University Hadassah Medical School
Shalev Itzkovitz: Weizmann Institute of Science

Nature Communications, 2020, vol. 11, issue 1, 1-12

Abstract: Abstract The intestinal epithelium is a structured organ composed of crypts harboring Lgr5+ stem cells, and villi harboring differentiated cells. Spatial transcriptomics have demonstrated profound zonation of epithelial gene expression along the villus axis, but the mechanisms shaping this spatial variability are unknown. Here, we combine laser capture micro-dissection and single cell RNA sequencing to uncover spatially zonated populations of mesenchymal cells along the crypt-villus axis. These include villus tip telocytes (VTTs) that express Lgr5, a gene previously considered a specific crypt epithelial stem cell marker. VTTs are elongated cells that line the villus tip epithelium and signal through Bmp morphogens and the non-canonical Wnt5a ligand. Their ablation is associated with perturbed zonation of enterocyte genes induced at the villus tip. Our study provides a spatially-resolved cell atlas of the small intestinal stroma and exposes Lgr5+ villus tip telocytes as regulators of the epithelial spatial expression programs along the villus axis.

Date: 2020
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DOI: 10.1038/s41467-020-15714-x

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